Previous Article | Next Article 
Infection and Immunity, December 2000, p. 6519-6525, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Human Lactoferrin Interacts with Soluble CD14 and Inhibits
Expression of Endothelial Adhesion Molecules, E-Selectin and
ICAM-1, Induced by the CD14-Lipopolysaccharide Complex
S.
Baveye,1
E.
Elass,1
D. G.
Fernig,2
C.
Blanquart,1
J.
Mazurier,1 and
D.
Legrand1,*
Laboratoire de Chimie Biologique et Unité Mixte de
Recherche n°8576 du Centre National de la Recherche Scientifique,
Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France,1 and
School of Biological Sciences, Life Sciences Building,
University of Liverpool, Liverpool L69 7ZB, United
Kingdom2
Received 22 February 2000/Returned for modification 15 May
2000/Accepted 8 September 2000
Lipopolysaccharides (LPS), either in the free form or complexed to
CD14, a LPS receptor, are elicitors of the immune system. Lactoferrin
(Lf), a LPS-chelating glycoprotein, protects animals against septic
shock. Since optimal protection requires administration of Lf prior to
lethal doses of LPS, we hypothesized that interactions between Lf and
soluble CD14 (sCD14) exist. In a first step, human sCD14 and human Lf
(hLf) were used to determine the kinetic binding parameters of hLf to
free sCD14 in an optical biosensor. The results demonstrated that hLf
bound specifically and with a high affinity (Kd = 16 ± 7 nM) to sCD14. Affinity chromatography studies showed that hLf interacted not only with free sCD14 but also, though with
different binding properties, with sCD14 complexed to LPS or lipid
A-2-keto-3-deoxyoctonic acid-heptose. In a second step, we have
investigated whether the capacity of hLf to interact with sCD14 could
modulate the expression of endothelial-leukocyte adhesion molecule 1 (E-selectin) or intercellular adhesion molecule 1 (ICAM-1) induced by
the sCD14-LPS complex on human umbilical vein endothelial cells
(HUVEC). Our experiments show that hLf significantly inhibited both
E-selectin and ICAM-1 expressions at the surface of HUVEC. In
conclusion, these observations suggest that the anti-inflammatory effects of hLf are due not only to the ability of the molecule to
chelate LPS but also to its ability to interact with sCD14 and with the
sCD14 complexed to LPS, thus modifying the activation of endothelial cells.
*
Corresponding author. Mailing address: Laboratoire de
Chimie Biologique, UMR CNRS 8576, Université des Sciences et
Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France. Phone:
33 3 20 33 72 38. Fax: 33 3 20 43 65 55. E-mail:
Dominique.Legrand{at}univ-lille1.fr.
Infection and Immunity, December 2000, p. 6519-6525, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Moreno-Navarrete, J. M., Ortega, F. J., Bassols, J., Ricart, W., Fernandez-Real, J. M.
(2009). Decreased Circulating Lactoferrin in Insulin Resistance and Altered Glucose Tolerance as a Possible Marker of Neutrophil Dysfunction in Type 2 Diabetes. J. Clin. Endocrinol. Metab.
94: 4036-4044
[Abstract]
[Full Text]
-
Kuo, C.-W., Chen, C.-M., Lee, Y.-C., Chu, S.-T., Khoo, K.-H.
(2009). Glycomics and Proteomics Analyses of Mouse Uterine Luminal Fluid Revealed a Predominance of Lewis Y and X Epitopes on Specific Protein Carriers. Mol. Cell. Proteomics
8: 325-342
[Abstract]
[Full Text]
-
de la Rosa, G., Yang, D., Tewary, P., Varadhachary, A., Oppenheim, J. J.
(2008). Lactoferrin Acts as an Alarmin to Promote the Recruitment and Activation of APCs and Antigen-Specific Immune Responses. J. Immunol.
180: 6868-6876
[Abstract]
[Full Text]
-
Puddu, P., Carollo, M. G., Belardelli, F., Valenti, P., Gessani, S.
(2007). Role of endogenous interferon and LPS in the immunomodulatory effects of bovine lactoferrin in murine peritoneal macrophages. J. Leukoc. Biol.
82: 347-353
[Abstract]
[Full Text]
-
Blais, D. R., Vascotto, S. G., Griffith, M., Altosaar, I.
(2005). LBP and CD14 Secreted in Tears by the Lacrimal Glands Modulate the LPS Response of Corneal Epithelial Cells. IOVS
46: 4235-4244
[Abstract]
[Full Text]
-
Naot, D., Grey, A., Reid, I. R, Cornish, J.
(2005). Lactoferrin - A Novel Bone Growth Factor. Clin Med Res
3: 93-101
[Abstract]
[Full Text]
-
Grey, A., Banovic, T., Zhu, Q., Watson, M., Callon, K., Palmano, K., Ross, J., Naot, D., Reid, I. R., Cornish, J.
(2004). The Low-Density Lipoprotein Receptor-Related Protein 1 Is a Mitogenic Receptor for Lactoferrin in Osteoblastic Cells. Mol. Endocrinol.
18: 2268-2278
[Abstract]
[Full Text]
-
Cornish, J., Callon, K. E., Naot, D., Palmano, K. P., Banovic, T., Bava, U., Watson, M., Lin, J.-M., Tong, P. C., Chen, Q., Chan, V. A., Reid, H. E., Fazzalari, N., Baker, H. M., Baker, E. N., Haggarty, N. W., Grey, A. B., Reid, I. R.
(2004). Lactoferrin Is a Potent Regulator of Bone Cell Activity and Increases Bone Formation in Vivo. Endocrinology
145: 4366-4374
[Abstract]
[Full Text]
-
Takayama, A., Satoh, A., Ngai, T., Nishimura, T., Ikawa, K., Matsuyama, T., Shimauchi, H., Takada, H., Sugawara, S.
(2003). Augmentation of Actinobacillus actinomycetemcomitans Invasion of Human Oral Epithelial Cells and Up-Regulation of Interleukin-8 Production by Saliva CD14. Infect. Immun.
71: 5598-5604
[Abstract]
[Full Text]
-
Van Amersfoort, E. S., Van Berkel, T. J. C., Kuiper, J.
(2003). Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock. Clin. Microbiol. Rev.
16: 379-414
[Abstract]
[Full Text]
-
Takayama, Y., Takahashi, H., Mizumachi, K., Takezawa, T.
(2003). Low Density Lipoprotein Receptor-related Protein (LRP) Is Required for Lactoferrin-enhanced Collagen Gel Contractile Activity of Human Fibroblasts. J. Biol. Chem.
278: 22112-22118
[Abstract]
[Full Text]
-
Uehara, A., Sugawara, S., Watanabe, K., Echigo, S., Sato, M., Yamaguchi, T., Takada, H.
(2003). Constitutive Expression of a Bacterial Pattern Recognition Receptor, CD14, in Human Salivary Glands and Secretion as a Soluble Form in Saliva. CVI
10: 286-292
[Abstract]
[Full Text]
-
Augusto, L. A., Synguelakis, M., Johansson, J., Pedron, T., Girard, R., Chaby, R.
(2003). Interaction of Pulmonary Surfactant Protein C with CD14 and Lipopolysaccharide. Infect. Immun.
71: 61-67
[Abstract]
[Full Text]
-
Caccavo, D., Pellegrino, N. M., Altamura, M., Rigon, A., Amati, L., Amoroso, A., Jirillo, E.
(2002). Review: Antimicrobial and immunoregulatory functions of lactoferrin and its potential therapeutic application. Innate Immunity
8: 403-417
[Abstract]
-
Gomez, H. F., Ochoa, T. J., Herrera-Insua, I., Carlin, L. G., Cleary, T. G.
(2002). Lactoferrin Protects Rabbits from Shigella flexneri-Induced Inflammatory Enteritis. Infect. Immun.
70: 7050-7053
[Abstract]
[Full Text]
-
Elass, E., Masson, M., Mazurier, J., Legrand, D.
(2002). Lactoferrin Inhibits the Lipopolysaccharide-Induced Expression and Proteoglycan-Binding Ability of Interleukin-8 in Human Endothelial Cells. Infect. Immun.
70: 1860-1866
[Abstract]
[Full Text]